7. Project Summary/Abstract Myeloproliferative neoplasms (MPNs) are chronic blood disorders that that can cause severe symptoms and early death. New treatments have become available recently that help ameliorate symptoms, but they do not reliably slow or halt disease progression. We seek to better understand what drives disease development and progression in MPNs, so that we can develop better therapies for patients with these diseases. Our preliminary data indicates that a signaling pathway called the NFkB pathway is abnormally activated in MPNs. We hypothesize that this pathway contributes to the development and progression of MPNs. Therefore, we have proposed a combination of mouse and human studies to determine how the NFkB pathway contributes to MPN pathogenesis, and to evaluate whether inhibition of NFkB signaling may have potential therapeutic benefits for MPN patients.